Congener of carbamazepine, only glucoronide conjugated not oxidized. Toxic effect due to epoxide are avoided risk of hepatotoxicity is less but hyponetrimia is more

Large number of BZDs have antiseizure properties but only few are used or approved

BDZs can be used orally but practically in therapeutics maximum use is IV. Redistribution like other lipid soluble drugs, central effect will be rapid but wanes soon. Redistribution half life – 1 hr NDD acts as partial agonist.

Because of the adverse effects it may require to withdraw or reduce the dosage

Lorazepam has more sustained effect. Diazepam action is short.

GABA agonist because of high lipid solubility

Structure and amino acid sequence is similar to L type of voltage sensitive Ca++ channel

1. CBZ, Phenytoin and valproate has been traditionally used in these conditions. CBZ is preferred nyoung girls bcoz of toxicities of phenytoin. Valproate should be used cautiously bcoz of hepatotoxicity. However newer drugs can be used 2. Absence seizure – equally effective but valproate is used more to prevent kindling and GTCS Mixed absence and GTCS is more common than pure absence. 3. Carbamazepine is preferred drug in complex partial seizure. Newer drugs can also be used

Monotherapy should be instituted. If a drug fails to control seizures adequately even after administration of maximum tolerated dose then alternate with other drug. Combination therapy should be instituted with drugs of different mechanism of actions – for example – Na+ channel blockers with GABA drugs etc. Pharmacokinetic interactions are common among antiseizure drugs – dose adjustment is necessary. 5. Febrile convulsion – in children under 5 yrs, convulsions during fever. May become chronic everytime fever developes.

Though antiseizure drugs have teratogenic effects and other birth defects, it should not be stopped as there is increased incidence of status epilepticus. Antiseizure drugs that induce CYPs have been associated with vit. K deficiency in newborn which can result in coagulopathy and haemorrhage. Therefore treatment of epilepsy during pregnancy should be supplemented with 10mg/day of vit.k

Transcript of "Antiepileptics"

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Antiepileptic Drugs Department of Pharmacology NEIGRIHMS, Shillong

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SOME FAMOUS PEOPLE WHO WERE AFFLICTED <ul><ul><ul><li>ALEXANDER THE GREAT </li></ul></ul></ul><ul><ul><ul><li>JULIUS CAESAR </li></ul></ul></ul><ul><ul><ul><li>NAPOLEON </li></ul></ul></ul>

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What are Epilepsies? <ul><li>Group of disorders of the CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizure) of loss of consciousness, with or without characteristic body movements (convulsions), sensory or psychiatric phenomena. </li></ul>

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What are seizures? <ul><li>A seizure is a transient alteration of behaviour due to the disordered, synchronous, and rythmic firing of populations of brain neurones. Seizure can be nonepileptic and can be evoked in normal brain </li></ul><ul><li>A seizure is a paroxysmal behavioral spell generally caused by an excessive disorderly discharge of cortical nerve cells. </li></ul>

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What are Epilepsies – Clinically? <ul><li>Epilepsy is a syndrome of two or more unprovoked or recurrent seizures on more than one occasion. </li></ul><ul><li>Epileptic seizures range from clinically undetectable (electrographic seizure) to convulsions. </li></ul>

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Generalized Seizures – contd. <ul><li>C. Atonic Seizures: </li></ul><ul><li>Unconsciousness with relaxation of all muscles </li></ul><ul><li>Patient falls down </li></ul><ul><li>Loss of postural tone, with sagging of the head or falling </li></ul><ul><li>D. Myoclonic Seizures: </li></ul><ul><li>Isolated clonic jerks associated with brief bursts of multiple spikes in the EEG </li></ul><ul><li>Momentary contractions of muscles of limbs or whole body </li></ul><ul><li>No loss of postural control </li></ul>

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2. Partial (focal) Seizures <ul><li>A. Simple partial seizure </li></ul><ul><li>Lasts for 20 – 60 seconds </li></ul><ul><li>Confined to a group of muscles or localized sensory disturbances depending on area of cortex involved </li></ul><ul><li>For example – if motor cortex of the left thumb then jerking movement of left thumb, and if it is sensory cortex then paresthesia of left thumb. </li></ul><ul><li>No alteration of consciousness </li></ul>

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Status epilepticus <ul><li>Continuous seizure activity for more than 30 minutes, or 2 or more seizures without recovery of consciousness. </li></ul><ul><li>Emergency: Recurrent tonic-clonic convulsions without recovery in between. </li></ul>

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Treatment of Epilepsies <ul><li>Aim of the treatment: </li></ul><ul><ul><li>Control and prevent all seizure activity (seizure - freedom and improvement in quality of life!) </li></ul></ul><ul><ul><li>To search the cause of epilepsy </li></ul></ul><ul><ul><li>Attempts to remove the causes </li></ul></ul><ul><ul><li>Symptomatic treatment with antiepileptic drugs </li></ul></ul><ul><ul><li>To consider status epilepticus as medical emergency and treat efficiently and promptly </li></ul></ul><ul><li>Choice of Drugs: According to the seizure types. </li></ul>

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Treatment of Epilepsies – contd. <ul><li>3. Initiation of treatment: </li></ul><ul><ul><li>Initiate therapy even if it is isolated tonic-clonic seizure with family history of seizure, abnormal neurological examination, abnormal EEG and an abnormal MRI </li></ul></ul><ul><ul><li>Treat with monotherapy </li></ul></ul><ul><ul><li>Substitute another drug if fails </li></ul></ul><ul><ul><li>Combination therapy – only when all monotherapy fail </li></ul></ul><ul><ul><li>Therapeutic monitoring of drugs – dose adjustments </li></ul></ul>

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Generalized Onset Seizures <ul><li>Tonic-clonic, myoclonic, and absence seizures: 1st line drug is usually valproate </li></ul><ul><li>Generalized seizures: Phenytoin and carbamazepine are effective on tonic-clonic seizures but not other types of seizures </li></ul><ul><li>Absence seizures: Valproate and ethosuximide are equally effective in children, but only valproate protects against the tonic-clonic seizures that sometimes develop. </li></ul><ul><li>Risk of hepatoxicity with valproate—should not be used in children under 2 </li></ul>

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Partial Onset Seizures <ul><li>Without generalization </li></ul><ul><ul><li>Phenytoin and carbamazepine may be slightly more effective </li></ul></ul><ul><li>With secondary generalization </li></ul><ul><ul><li>First-line drugs are carbamazepine and phenytoin (equally effective) </li></ul></ul><ul><ul><li>Valproate, phenobarbital, and primidone are also usually effective </li></ul></ul><ul><li>Phenytoin and carbamazepine can be used together (but both are enzyme inducers) </li></ul>

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Status Epilepticus <ul><li>Defn.: Continuous seizure activity for more than 30 minutes, or 2 or more seizures without recovery of consciousness. Recurrent tonic-clonic convulsions without recovery in between </li></ul><ul><li>Goal of therapy: rapid termination of seizure activity – more difficult to control – permanent brain damage </li></ul><ul><li>Prompt treatment with effective Drugs </li></ul><ul><li>Attention to hypoventilation and hypotension </li></ul><ul><li>Treatment is IV only </li></ul>